CRITICAL ISSUES IN PERIODONTAL

RESEARCH

By
Dr Sphoorthi Anup Belludi
Professor in department of Periodontics
K.L.E Society’s Institute of Dental Sciences, Bengaluru
INTRODUCTION
 CRITICAL ISSUES

EPIDEMIOLOGY

MICROBIOLOGY/ETIOLOGY

PATHOGENESIS

DIAGNOSIS

TREATMENT THERAPY

IMPLANTS

STATISTICS

ETHICS

RESEARCH
• The clinical discipline we call periodontology has come a long way. Concepts
and procedures for the treatment of periodontal diseases are scientifically
based, well-defined, and generally adopted and applied by clinicians.

• Rational measures to prevent these diseases are available and widely practiced
in industrialized societies. The goal of virtually eliminating periodontal
diseases as a public health problem seems not only feasible but probable for
the large majority in most populations" (Loe, 1993).

STILL MANY UNRESOLVED PROBLEMS REMAIN

 EPIDEMIOLOGY/
PREVALENCE

• Investigations into the nature of periodontal diseases began in the early

1960’s.

• In 1950‟s-60‟s, indices used to measure periodontal disease were

Periodontal Index of Russell (1967), and The Periodontal Disease Index of
Ramfjord (1967) .
 EPIDEMOLOGIC STRATEGIES
• POPULATION STRATEGY – Community wide approach-
change unfavourable behaviour
• SECONDARY PREVENTION STRATEGY – Detecting &
treating individuals
• IDENTIFICATION OF HIGH RISK GROUPS – early detection
of active disease & subjects
MARSHALL-DAY ET AL. 1955
• The picture was one of almost universal prevalence in adults.

• It was widely accepted that once periodontitis was initiated, if left untreated it
progressed inexorably in a continuous and linear manner until tooth loss
occurred (Greene, 1963).

• A very different picture began to emerge from studies conducted in

subsequent decades.
 Brown et al 1990

attachment loss of 5 mm or > --- < 1 % all sites studied.

deep pockets < 1% of the sample studied
• These studies demonstrated a prevalence much lower than expected with
severe periodontitis observed in a very small proportion of population.

• The most well known study presented is the National Health and Nutrition
Examination Survey studies covering the years in 1988-1994 and repeated in
1999-2000. The results shows that the prevalence of periodontitis for
NHANES in 1988-94 is 7.3% and for 1999-2000 it is 4.2%.

IS THE PREVALENCE CHANGING?

• Resolution of this issue is critical since changes in the prevalence of disease
impact dental education, indivdidual and group practices, manpower needs
and Government and other public health programs.

• Another unexpected observation came from studies of populations in third

world countries.
• Individuals with less plaque & calculus – less incidence of periodontitis.

Baelum et al 1986
-Villagers in Zanzibar & Pemba islands (Tanzania)
• - High levels of plaque & calculus
• - less than 10% with 5mm or > attachment loss
• - less than 10% of sample with 3mm or deeper pockets

• Similar results have been found in a study by Reddy et al 1986 (South

Africa)
• It is now clear that only a small proportion of population studied has been afflicted
with the disease.

Second unresolved critical issue is to determine-

• Identity & characteristics of this section (determination of prevalence in population

subgroups or identification of highly susceptible groups of individuals).

• Identification of determinants of disease resistance.

• Third critical issue is to determine the validity of concept
• Good oral hygiene = periodontal health?
• Poor or no oral hygiene = severe periodontitis?
(Brown & Reddy 1986)
Severe plaque and calculus was found with no gross periodontal disease in
studies by Baelum (1986) and Reddy et al 1986 . Such studies show a
complex relationship between OH and periodontal status.

Only bacteria might not be responsible for disease, other factors need to be
considered like Host-relationship (Offenbacher, 1980), Environment (Marsh,
1986), Genetics (Kornman, 2008).
 SUMMARY

1. Is the prevalence of periodontitis changing?

2. Determination of the identity and characteristics of the

population affected with severe periodontitis

3. Determine the validity of the concept that good oral

hygiene equates to periodontal health while poor or no
oral hygiene results in a high prevalence of severe
periodontitis.
 MICROBIOLOGY/
ETIOLOGY

Jordan & Keyes (1964)

Periodontitis : an infectious transmissible disease in rodents.

Loe & Coworkers (1965)

First direct evidence , human study (classic experimental gingivitis study)

Lindhe et al (1975)- animal model, periodontitis is of bacterial origin

Major accomplishments in the area of microbiology have been
reviewed and summarized by Haffajee and Socransky, 1994
An obvious critical issue is whether a dozen or more microbial species are in fact
involved in a meaningful way in the etiology of human periodontitis.

There may be only one or, at most, two species essential for the initiation of
periodontitis, while the other species may be innocent bystanders, or may
participate in propagation of lesions once initiated.
• Multiple species of bacteria may share a common characteristic or factor :
Lipopolysaccharides
McCoy et al 1987

If LPS plays a role central to pathogenesis as suggested , exact species of

bacteria involved may be irrelevant.
 Periodontitis : A)consequence of overgrowth of commensals or an B)exogenous
origin?

• If it is due to overgrowth of commensal flora then- Transmission not an issue

• In contrast if bacteria must be acquired for infection to occur, then

transmission is a key issue.
• There is strong evidence that A.a and P. gingivalis are transmitted among
family members and between spouses (Saarela et al., 1993; van Steenberge et
al., 1993).

• A. actinomycetemcomitans from the family pet dog to a child. (Preus and

Olson, 1988).

• If transmission is an essential step in spread of disease, our approach to

treatment may change from focus on patient to infected families.
Question of the relationship between the presence of a "pathogenic"
flora and disease status.

There is strong evidence that putative periodontal pathogens can be found

commonly in periodontally normal individuals (Dahlen et al 1989) and at
healthy sites in mouths of periodontally diseased individuals( Socransky et al
1991).
• Haffajee and Socransky (1994) have shown that thresholds exist below which
periodontal sites, even though colonized by a given pathogen, are disease
inactive, but above which disease activity is observed.

• The threshold for disease activity for P. gingivalis appears to be about 5 x 10⁵,
and that for A. actinomycetemcomitans just over 10⁴ bacterial counts.
• Various strains of periodontopathic bacteria such as P. gingivalis differ greatly
with regard to virulence and pathogenicity
(Marsh et al., 1989; Neiders et al., 1989;
Shah et al., 1989; Smalley et al.1989;
Socransky and Haffajee, 1991, 1992).

Real association between presence of

pathogenic flora and disease status
cannot be resolved
• There is evidence that local environmental factors may be major determinants
of virulence.
• For example, the concentration of iron is a major determinant of the
production of certain cell-envelope proteins that may be important virulence
factors (McKee et al., 1986; Barua et al., 1990; Bramanti et al., 1993).
• Other factors
• temperature, pH,
• the concentration of ions such as calcium and magnesium may also participate
in regulation of gene expression.

Most aspects of the role of environmental factors remain obscure

 SUMMARY
1. Whether a dozen or more microbial species are in fact
involved in a meaningful way in the etiology of human
periodontitis.
2. Whether periodontal infections are a consequence of
overgrowth of commensal periodontal microflora or
exogenous infections.
3. The relationship between the presence of a "pathogenic"
flora and disease status.
4. The role that environment and ecology play in bacterial
gene expression, genetic change, and virulence.
 PATHOGENESIS :

1960S : FOCUS ON THE BACTERIAL EFFECT ON THE HOST

1970S : FOCUS ON THE HOST FACTOR

• Ivanyi and Lehner (1970)- Peripheral blood mononuclear cells were

sensitised to antigens of infecting bacteria

• Lavine (1976)- discovery of defective neutrophils (less chemoattractant

reaction)
• While in 1970s investigators interested in role of host defense mechanisms
focused on T cells and possible cell- mediated hypersensitivity mechanisms,
in the 1980s the possible role and importance of B cells and the humoral
immune response became a focus.

• This was made possible in part by application of ELISA to research.

 Enormous advances were made in 1980s in our
understanding of mechanism of tissue destruction in
periodontitis
Page 1991; Birkedal-Hansen 1993
• Critical issue – Understanding pathogenesis and a Deeper understanding into
the role of Host modulation

• Advances in our understanding of pathogenesis of periodontitis have major

implications for development of future therapies

• Over time, we will undoubtedly develop ways to control gene activation, and
thereby block destruction of the periodontal tissues.
 ISSUES RELATED TO DIAGNOSIS

Diagnostic procedures may be used to identify people at risk of developing

disease (at risk), detect early stage disease in clinically asymptomatic individuals
(screening), classify disease categories (classification), predict likely responders
to specific treatments (treatment planning), monitor treatment efficacy and detect
disease recurrence (monitoring).
• The quality of the data derived from clinical trials depends on the experience,
knowledge and skills of the clinical examiner(s) who are evaluating the
patients.

• There is a lack of training and calibration of clinical examiners for accurate

diagnosis

• Many of the scoring systems used (such as plaque and gingival indices) are
somewhat subjective and there is much scope for interpretation of the scoring
criteria by the clinician. Objective scores like probing depths and recession
are subject to error by position of probes and reading of scores.
 Various attempts have been made to conquer these problems such as

• Calibration of examiners: In reference to a fixed scale or a defined set of

standards, or even a gold standard
• Gold standard clinician is experienced, knowledgeable and they have low
variability in their repeated measures. But cannot be always precise and
accurate
• Concept of “Examiner Alignment and Assessment” - Training protocol given
by Hefti and Preshaw.
• Diagnosis of disease activity is the next issue in hand. Concept in 1960‟s-
1970‟s was that once pocket is formed, disease progresses linearly and
continuously to cause eventual loss of tooth.

• This concept served as basis for surgical elimination of pockets as the

appropriate goal for therapy.

• Beginning in the 1980s, several longitudinal studies were performed on

untreated patients(Lindhe et al., Jenkins et al 1988).
• In the 1980‟s, it was said that disease progression found to be rather episodic,
site specific, and infrequent.

• Indeed, in patients with early to moderate as well as in those with advanced

disease, only roughly 3% to 10% of sites worsened, and most deteriorating
sites occurred in a small proportion of patients.

• These were totally unexpected results, which mandated a major change in our
concept of the nature of periodontal diseases.
• Using conventional diagnostic aids assessment like pocket depth, attachment
level, bleeding, radiographic manifestations of alveolar bone loss, we are
unable to distinguish between active and inactive pockets.

• Inability to make the distinction between diseased/ disease active and

healthy/ disease in-active pockets is the central critical issue in periodontitis.

• Hence the need for large research effort aimed at development of diagnostic
methods capable of detecting disease-active sites. Advanced diagnostic aids in
microbial diagnosis can be utilized which have shown promising results.
Identification of risk indicators and factors is of enormous
importance in diagnosis and treatment planning of periodontitis
patients.

Risk indicators (according to R.C.Page)

 SUMMARY

1. Training and calibration of clinical examiners for

accurate diagnosis

2. To make the distinction between diseased/ disease active

and healthy/ disease in-active pockets

3. Adequate evidence-based understanding of association

of risk factors with periodontal disease
 ISSUES RELATED TO THERAPY

NON-SURGICAL THERAPY

• Thoroughness of debridement of the tooth roots of microbial deposits was a

more important determinant of the final therapeutic outcome .

• Hence arose the concept of scaling and root planning.

• An era of adjunctive chemotherapy using systemically administered
antibiotics slowly gained popularity. Different obstacles faced by the
researchers were the choice of drugs to be used amongst the wide array
of available products. Substantivity of these drugs became a debatable
issue even after using it for periodontal therapy.

• Lindhe et al. (1984) claimed that surgical therapy formed an essential

part of the treatment plan, thus making the non-surgical methods take a
back seat.
 ISSUES RELATED TO SURGICAL THERAPY

• Surgical therapy aimed at elimination of periodontal pockets and restoration

of the normal physiological contour to the marginal alveolar bone came into
widespread use in the 1960's.

• In the 1970's, these surgical techniques were honed to perfection. While

surgical treatments were effective in arresting the progress of periodontal
tissue destruction in most patients, some clinicians and investigators began to
question whether surgery was in fact necessary (Knowles et al., 1979).
 ISSUES RELATED TO REGENERATION THERAPY

• First, the approaches we have relied on most for regeneration of periodontal

tissues are various grafting procedures and guided-tissue regeneration.

• These have been moderately successful.

• These procedures usually fail at those sites where we do not have other
treatments that do succeed, and are successful in those cases where other
treatments are available (Page, 1993).
• Outcomes of various grafting procedures in Guided Tissue regeneration are
unpredictable. There is a need of extensive basic and clinical research aimed
at improving the success rate.

• Lack of understanding of why some patients fail to respond favorably to any

form of periodontal therapy is seen.

• A critical issue that the clinicians face is - whether periodontitis patients

produce antibodies to their infecting bacteria and if not, why? If so, are they
protective and if not, why?
• Studies have shown that roughly half of young adults with severe
periodontitis fail to produce serum antibodies to the infecting bacteria (Chen
et al., 1991; Whitney et al., 1992).

• In those who do, the antibodies are not effective in opsonization and in
enhancing phagocytosis and killing of bacteria (Chen et al., 1991; Sjbstrom et
al).
• Treatment by scaling and root planing is known to result in bacteremia. It was
suspected that such treatment could be a form of vaccination.

• Idea was tested and demonstrated that treatment activates an immune

response in those individuals who were previously seronegative, and the
induced antibodies are more effective in enhancing phagocytosis and killing
than those produced during the course of spontaneous infection (Chen et al.,
1991)
• A Macaca fascicularis nonhuman primate model to test the idea.

• Experimental periodontitis was induced in monkeys and demonstrated that

immunization using a vaccine containing a killed periodontal pathogen could
arrest destruction of alveolar bone (Persson et al., 1994).

• One of the important critical issue is to achieve an understanding of the role

that the host defense mechanisms, especially the immune response, play in
periodontitis, and to determine whether immunization is an effective
treatment and preventive measure. (chen et al. 1991, Whitney et al. 1992).
 SUMMARY
1. Are the current surgical and regenerative techniques
plausible
2. Selection of the techniques
3. Inability to identify the patients who fail to respond to
treatment prior to treatment, and we have no
understanding of the reasons they fail to respond
favorably
4. Will Immunization be an effective treatment and
preventive measure
 IMPLANTS OR TEETH?

• Factors to be considered while placing implants for replacement of missing

teeth include quality of life, esthetics, cost and attitude of patients (as well as
many dentists).

• There is a common thinking that - once an implant is placed, all worries

about oral health are gone.

• But an increasing incidence of peri-implantitis is often experienced by the

clinicians. Varying concepts of pathogenesis of peri-implantitis are proposed.
 Critical Issue

Implants / Save Natural teeth

 ISSUES IN STATISTICS

• Statistics is a completely different world, with its own language, rules

and regulations. Dental researchers and statisticians generally existed in
isolation, perhaps interfacing only occasionally, usually with limited
understanding on both sides.

• Biostatisticians are breaking the barriers between clinicians, researchers

and statisticians. They have knowledge of, and interest in, dental and
periodontal research. Statistics is not just a testing process, it is a
thinking process.
 ETHICAL ISSUES

• In clinical trials, there are failures to obtain Institutional Review Board

approval.

• Plagiarism amongst the members involved in the study or outside is rampant.

• Lack of co-ordination between Animal ethical review board and clinical

researchers, non-availability of animals and strict rules and regulations due to
advent of animal rights are seen. Ill-treatment of animals leads to no definite
assessment of intervention.

• Non publishing of potentially useful data is also one of the critical issues.
• Theoretically, the informed consent process ensures that research subjects are
well informed as to the study purpose, potential risks, potential benefits and
alternatives to participation.

• Meticulous evaluation of dissertations should be done in Dental institutions.

Studies have to be subjected to meta-analysis and published in accessible
reputed journals. Results can be deciphered by proper orientation of students
and staff through basic training and screening of research for authenticity and
appropriate utilization of funds
 ISSUES IN RESEARCH

• Randomized clinical trials are the gold standard by which effectiveness of

various treatments or interventions are determined.

• However, the method by which this is achieved raises the question as to

whether clinical research is good for the participants.
• When the efficacy of a treatment is assessed in RCT, patient preference is
seldom taken into account.

• Preference expressed by either the patient or clinician may impact the validity
of a RCT.

• Randomizing patients to treatments they do not want may reduce their

participation, follow-up and satisfaction, and thereby lead to poor outcomes.
• Hewison & Haines argue that limitations imposed by Research Ethics
Committees that allow investigators to only approach patients who opt in
(respond positively to invitational letters to participate in research) fails to
create unbiased samples and undermines the accurate estimation of outcomes.
• Most funding agencies, including the National Institute of Dental and
Craniofacial Research, are unlikely to support an application for a randomized
clinical trial unless the investigative team can show through pilot work that
the approach is likely to succeed.

• The presence of a statistically significant difference between groups is a

primary measure of treatment effectiveness, as viewed by journal reviewers
and by agencies such as the Food and Drug Administration, which regulate
claims of devices and products used to improve oral health.
• This factor makes it possible to game a randomized clinical trial to produce
statistically significant results, even when the difference between groups is
small or not clinically important.

• Even when randomized clinical trials are well designed, clinical

meaningfulness and usefulness remain issues for consideration by researchers
and subjects alike.
 CONCLUSION
• A definite collaborative strategy could bring about radical changes
in the public perception and understanding of periodontal research.

• Periodontal research in India has to create its own identity in the

global scenario.

• The ultimate aim of the research should be to benefit the so called

'common man'
 REFERENCES
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2012;59:7-13.
• Brown LJ, Löe H. Prevalence, extent, severity and progression of periodontal
disease. Periodontol 2000 1993;2:57-71.
• Page RC. Milestones in periodontal research and the remaining critical issues. J
Periodontal Res 1999;34:331-9.
• Loe H, Theilade E, Jensen SB. Experimental gingivitis in man. J Periodontol
1965;36:177-87.
• Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal
diseases. Periodontol 2000 1994;5:78-111.
• Kumar M, Pant V.A, Govila V, Sharma M. Critical issues in Periodontal Research. J
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